Systems for providing non-invasive neurorehabilitation of a patient

ABSTRACT

A system for providing non-invasive neuromodulation to a patient includes a mouthpiece and a controller. The mouthpiece includes an elongated housing, a printed circuit board, control circuitry mounted within the elongated housing, and a cable for connecting to a controller. The controller includes an elongated u-shaped element, an electronic receptacle, and a microcontroller. A method for providing non-invasive neurorehabilitation of a patient including connecting a mouthpiece to a controller, transmitting a numeric sequence to the mouthpiece, generating a first hash code, transmitting the first hash code to the controller, generating a second hash code, comparing the second hash code with the first hash code, enabling electrical communication between the mouthpiece and the controller only if the first hash code matches the second hash code, contacting the mouthpiece with the patient&#39;s intraoral cavity, and delivering neurostimulation to the patient&#39;s intraoral cavity.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/727,100, filed Jun. 1, 2015, now U.S. Pat. No. 9,616,222, which is acontinuation-in-part of U.S. patent application Ser. No. 14/558,768,filed Dec. 3, 2014, now U.S. Pat. No. 9,072,889, both of which areincorporated by reference herein in their entireties.

FIELD OF THE INVENTION

In general, the invention relates to devices and methods fornon-invasive neurostimulation of a subject's brain. More specifically,the invention relates to devices and methods for non-invasiveneurostimulation of a subject's brain to effect treatment of variousmaladies.

BACKGROUND OF THE INVENTION

Traumatic brain injury (TBI) is a leading cause of disability around theworld. Each year in the United States, about two million people suffer aTBI, with many suffering long term symptoms. Long term symptoms caninclude impaired attention, impaired judgment, reduced processing speed,and defects in abstract reasoning, planning, problem-solving andmultitasking.

A stroke is a loss of brain function due to a disturbance in the bloodsupply to the brain. Every year, about 800,000 people in the UnitedStates will have a stroke. Stroke is a leading cause of long-termdisability in the United States, with nearly half of older strokesurvivors experiencing moderate to severe disability. Long term effectscan include seizures, incontinence, vision disturbance or loss ofvision, dysphagia, pain, fatigue, loss of cognitive function, aphasia,loss of short-term and/or long-term memory, and depression.

Multiple sclerosis (MS) is a disease that causes damage to the nervecells in the brain and spinal cord. Globally, there are about 2.5million people who suffer from MS. Symptoms can vary greatly dependingon the specific location of the damaged portion of the brain or spinalcord. Symptoms include hypoesthesia, difficulties with coordination andbalance, dysarthria, dysphagia, nystagmus, bladder and boweldifficulties, cognitive impairment and major depression to name a few.

Alzheimer's disease (AD) is a neurodegenerative disorder affecting over25 million people worldwide. Symptoms of AD include confusion,irritability, aggression, mood swings, trouble with language, and bothshort and long term memory loss. In developed countries, AD is one ofthe most costly diseases to society.

Parkinson's disease (PD) is a degenerative disorder of the centralnervous system, affecting more than 7 million people globally. Symptomsof PD include tremor, bradykinesia, rigidity, postural instability,cognitive disturbances, and behavior and mood alterations.

One approach to treating the long term symptoms associated with TBI,stroke, MS, AD, and PD is neurorehabilitation. Neurorehabilitationinvolves processes designed to help patients recover from nervous systeminjuries. Traditionally, neurorehabilitation involves physical therapy(e.g., balance retraining), occupational therapy (e.g., safety training,cognitive retraining for memory), psychological therapy, speech andlanguage therapy, and therapies focused on daily function and communityre-integration.

Another approach to treating the long term symptoms associated with TBI,stroke, MS, AD, and PD is neurostimulation. Neurostimulation is atherapeutic activation of part of the nervous system. For example,activation of the nervous system can be achieved through electricalstimulation, magnetic stimulation, or mechanical stimulation. Typicalapproaches focused mainly on invasive techniques, such as deep brainstimulation (DBS), spinal cord stimulation (SCS), cochlear implants,visual prosthesis, and cardiac electrostimulation devices. Only recentlyhave non-invasive approaches to neurostimulation become more mainstream.

Despite many advances in the areas of neurorehabilitation andneurostimulation, there exists an urgent need for treatments that employa combined approach, including both neurorehabilitation andneurostimulation to improve the recovery of patients having TBI, stroke,multiple sclerosis, Alzheimer's, Parkinson's or any other neurologicalimpairment.

SUMMARY OF THE INVENTION

The invention, in various embodiments, features methods and devices forcombining non-invasive neuromodulation with traditionalneurorehabilitation therapies. Clinical studies have shown that methodscombining neurostimulation with neurorehabilitation are effective intreating the long term neurological impairments due to a range ofmaladies such as TBI, stroke, MS, AD, and PD.

In one aspect, the invention features a system for providingnon-invasive neuromodulation to a patient. The system includes amouthpiece and a controller. The mouthpiece includes an elongatedhousing having an anterior region and a posterior region, the elongatedhousing having a non-planar exterior top surface. The mouthpiece alsoincludes a printed circuit board mounted to a bottom portion of theelongated housing, the printed circuit board having a plurality ofelectrodes for delivering subcutaneous local electrical stimulation tothe patient's tongue. The mouthpiece also includes control circuitrymounted within a top portion of the elongated housing for controllingelectrical signals delivered to the electrodes. The mouthpiece alsoincludes a cable with a first end attached to the anterior portion ofthe elongated housing and having a connector at a second end forconnecting to a controller, the cable delivering electrical current tothe electrodes via the control circuitry. The controller includes anelongated u-shaped element configured to rest upon a patient'sshoulders. The controller also includes an electronic receptacle locatedat a terminus of the u-shaped element connecting to the cable. Thecontroller also includes a microcontroller located within thethree-dimensional u-shaped element, the microcontroller configured tosend electrical control signals to the mouthpiece, the electricalcontrol signals determining an amplitude and duration of electricalsignals delivered to the patient's tongue.

In some embodiments, the system also includes an accelerometer formeasuring an activity level of the patient. In some embodiments, thesystem also includes a data logger for logging information related tothe activity level of the patient. In some embodiments, the system alsoincludes tongue sense circuitry for determining if a patient's tongue isin contact with the plurality of electrodes located on the bottomportion of the mouthpiece. In some embodiments, the system also includesa real time clock for determining a total time of usage of themouthpiece. In some embodiments, the system also includes a battery forproviding a current to the mouthpiece. In some embodiments, the systemalso includes an optical indicator that indicates a power level of thebattery. In some embodiments, the system also includes an audioindicator that can warn the patient when the remaining battery charge isinadequate to complete a therapy session. In some embodiments, theexterior top surface of the elongated housing is planar. In someembodiments, the printed circuit board is mounted to a middle or topportion of the elongated housing. In some embodiments, the controlcircuitry is mounted within a middle or top portion of the elongatedhousing. In some embodiments, the cable is permanently attached to thecontroller and is removably attached to the mouthpiece.

In another aspect, the invention features a system for providingnon-invasive neuromodulation to a patient. The system includes amouthpiece and a controller. The mouthpiece includes an elongatedhousing having an anterior region and a posterior region, the elongatedhousing having a non-planar exterior top surface. The mouthpiece alsoincludes a printed circuit board mounted to the elongated housing, theprinted circuit board having a plurality of electrodes for deliveringsubcutaneous local electrical stimulation to the patient's tongue. Themouthpiece also includes control circuitry mounted within the elongatedhousing for controlling electrical signals delivered to the electrodes.The mouthpiece also includes a first communication module deliveringelectrical current to the electrodes via the control circuitry. Thecontroller includes an elongated u-shaped housing configured to restupon a patient's shoulders. The controller also includes a secondcommunication module within the housing coupled to and in communicationwith the first communication module. The controller also includes amicrocontroller located within the housing and configured to exchangeelectrical signals with the mouthpiece, the electrical signalsdetermining an amplitude and duration of electrostimulation energypulses delivered to the patient's tongue.

In some embodiments, the system also includes an accelerometer formeasuring an activity level of the patient. In some embodiments, thesystem also includes a data logger for logging information related tothe activity level of the patient. In some embodiments, the system alsoincludes tongue sense circuitry for determining if a patient's tongue isin contact with the plurality of electrodes located on the bottomportion of the mouthpiece. In some embodiments, the system also includesa real time clock for determining a total time of usage of themouthpiece. In some embodiments, the system also includes a battery forproviding a current to the mouthpiece. In some embodiments, the systemalso includes an optical indicator that indicates a power level of thebattery. In some embodiments, the system also includes an audioindicator that can warn the patient when the remaining battery charge isinadequate to complete a therapy session.

In yet another aspect, the invention features a system for providingnon-invasive neuromodulation to a patient. The system includes amouthpiece. The mouthpiece includes an elongated housing having ananterior region and a posterior region, the elongated housing having anon-planar exterior top surface. The mouthpiece also includes a printedcircuit board mounted to a bottom portion of the elongated housing, theprinted circuit board having a plurality of electrodes for deliveringsubcutaneous local electrical stimulation to the patient's tongue. Themouthpiece also includes control circuitry mounted within a top portionof the elongated housing for controlling electrical signals delivered tothe electrodes. The system also includes a mobile device configured tosend electrical control signals to the mouthpiece, the electricalcontrol signals determining an amplitude and duration of electricalsignals delivered to the patient's tongue.

In some embodiments, the system also includes an accelerometer formeasuring an activity level of the patient. In some embodiments, thesystem also includes a data logger for logging information related tothe activity level of the patient. In some embodiments, the system alsoincludes tongue sense circuitry for determining if a patient's tongue isin contact with the plurality of electrodes located on the bottomportion of the mouthpiece. In some embodiments, the system also includesa real time clock for determining a total time of usage of themouthpiece. In some embodiments, the system also includes an audioindicator that can warn the patient when the remaining battery charge isinadequate to complete a therapy session.

In yet another aspect, the invention features a controller fordelivering electrical control signals to a mouthpiece during anon-invasive neuromodulation therapy session. The controller includes anelongated u-shaped element configured to rest upon a patient'sshoulders. The controller also includes an electronic receptacle locatedat a terminus of the three-dimensional u-shaped element for connectingto a cable. The controller also includes a microcontroller locatedwithin the three-dimensional u-shaped element, the microprocessorconfigured to send electrical control signals to the mouthpiece, theelectrical control signals determining an amplitude and duration ofelectrical signals delivered to the patient's tongue.

In some embodiments, the controller also includes an accelerometer formeasuring an activity level of the patient and a data logger for logginginformation related to the activity level of the patient. In someembodiments, the controller also includes an audio alarm for indicatingat least one of the end of a therapy session, a low electrical signaldelivered to the patient's tongue, activation/deactivation of thecontroller, or pausing of the electrical signals delivered to thepatient's tongue. In some embodiments, the controller also includes apower switch for activating and deactivating the controller and one ormore intensity buttons for controlling the intensity of electricalsignals delivered to the mouthpiece by the controller. In someembodiments, the controller also includes a display for presentinginformation and receiving input from the patient. In some embodiments,the controller also includes a battery for providing a current to themouthpiece. In some embodiments, the controller also includes a motorfor causing the u-shaped element to vibrate. In some embodiments, thecontroller also includes at least one printed circuit board for mountingelectrical isolation circuitry, battery management circuitry, and amicrocontroller, at least one printed circuit board for mounting a playbutton, a pause button, and the electronic receptacle, and at least onecircuit board for mounting one or more intensity buttons. In someembodiments, the controller also includes circuitry for sensing acurrent delivered to a patient's tongue via the mouthpiece. In someembodiments, the controller also includes a cable forming an integralportion of the mouthpiece.

In yet another aspect, the invention features a controller fordelivering electrical control signals to a mouthpiece during anon-invasive neuromodulation therapy session. The controller includes acoextensively dimensioned element configured to rest in proximity to apatient's face. The controller also includes a receptacle located at acentral portion of a first surface of the coextensively dimensionedelement, the receptacle providing an electrical and mechanicalconnection to the mouthpiece. The controller also includes a displaylocated on a second surface of the coextensively dimensioned element,the display providing visual indications to the patient. The controlleralso includes a microcontroller located within the coextensivelydimensioned element, the microcontroller configured to send electricalcontrol signals to the mouthpiece, the electrical control signalsdetermining an amplitude and duration of electrical signals delivered tothe patient's tongue.

In some embodiments, the controller also includes an accelerometer formeasuring an activity level of the patient and a data logger for loggingthe activity level of the patient, transmissions to or from thecontroller, the intensity of electrical signals delivered to themouthpiece, and information received circuitry configured to determineif the patient's tongue is in contact with the mouthpiece. In someembodiments, the controller also includes an audio alarm for indicatingat least one of the end of a therapy session, a low electrical signaldelivered to the patient's tongue, activation/deactivation of thecontroller, or pausing of the electrical signals delivered to thepatient's tongue. In some embodiments, the controller also includes apower switch for activating and deactivating the controller and one ormore intensity buttons located on a third surface of the coextensivelydimensioned element, the intensity buttons controlling the intensity ofelectrical signals delivered to the mouthpiece by the controller. Insome embodiments, the controller also includes a display for presentinginformation and receiving input from the patient. In some embodiments,the controller also includes a battery for providing a current to themouthpiece. In some embodiments, the controller also includes a motorfor causing the coextensively dimensioned element to vibrate. In someembodiments, the controller also includes at least one printed circuitboard for mounting electrical isolation circuitry, battery managementcircuitry, and a microcontroller, at least one printed circuit board formounting a play button and a pause button, at least one printed circuitboard for mounting the circuitry associated with the receptacle, and atleast one circuit board for mounting one or more intensity buttons. Insome embodiments, the controller also includes circuitry for sensing acurrent delivered to a patient's tongue via the mouthpiece.

In yet another aspect, the invention features a method for providingnon-invasive neurorehabilitation of a patient. The method includesconnecting a mouthpiece to a controller. The method also includestransmitting a numeric sequence generated by a first processor withinthe controller to the mouthpiece. The method also includes generating afirst hash code by a second processor within the mouthpiece, the firsthash code based on the received numeric sequence and a shared secret keystored in memory within the mouthpiece. The method also includestransmitting the first hash code from the mouthpiece to the controller.The method also includes generating a second hash code by the firstprocessor within the controller, the second hash code based on therandom number and the shared secret key. The method also includescomparing, by the first processor, the first hash code with the secondhash code. The method also includes enabling electrical communicationbetween the mouthpiece and the controller only if the first hash codematches the second hash code. The method also includes contacting themouthpiece with the patient's intraoral cavity. The method also includesdelivering neurostimulation to the patient's intraoral cavity, theneurostimulation being delivered by the controller via the mouthpiece.

In some embodiments, the method also includes connecting the mouthpieceto the controller via a cable. In some embodiments, the method alsoincludes providing power to the controller. In some embodiments, themethod also includes delivering electrical neurostimulation via anelectrode array to the patient's intraoral cavity.

In yet another aspect, the invention features a method for providingnon-invasive neurorehabilitation of a patient via a controller and amouthpiece. The method includes connecting the mouthpiece to thecontroller. The method also includes generating a first hash code basedon a unique serial number and a shared secret key. The method alsoincludes storing the unique serial number and the first hash code inmemory located in the mouthpiece. The method also includes transmittingthe first hash code and the unique serial number from the mouthpiece tothe controller. The method also includes generating a second hash codein a first processor in the controller, the second hash code based onthe unique serial number and the shared secret key. The method alsoincludes permitting electrical communication between the mouthpiece andthe controller only if the first hash code matches the second hash code.The method also includes contacting the mouthpiece with the patient'sintraoral cavity. The method also includes delivering neurostimulationto the patient's intraoral cavity, the neurostimulation being deliveredby the controller via the mouthpiece.

In some embodiments, the method also includes connecting the mouthpieceto the controller via a cable. In some embodiments, the method alsoincludes providing power to the controller. In some embodiments, themethod also includes delivering electrical neurostimulation via anelectrode array to the patient's intraoral cavity. In some embodiments,the first hash code is an SHA-256 hash code.

In yet another aspect, the invention features a mouthpiece for providingneurorehabilitation to a patient, the mouthpiece receiving electricalneurostimulation signals from a controller and selectively deliveringthe received electrical neurostimulation signals to the patient. Themouthpiece includes an elongated housing having an anterior region and aposterior region, the elongated housing having a non-planar exterior topsurface. The mouthpiece also includes a printed circuit board mounted toa bottom portion of the elongated housing, the printed circuit boardhaving a plurality of electrodes for delivering subcutaneous localelectrical stimulation to the patient's tongue. The mouthpiece alsoincludes control circuitry mounted within a top portion of the elongatedhousing for controlling electrical signals delivered to the electrodes.The mouthpiece also includes a memory mounted within a top portion ofthe elongated housing. The mouthpiece also includes a processor mountedwithin the top portion of the elongated housing, the processorconfigured to (i) receive a numeric sequence from the controller, (ii)generate a first hash code based on the received numeric sequence and ashared secret key stored in the memory, (iii) transmit the first hashcode to the controller, (iv) receive communications from the controlleronly if a second hash code based on the numeric sequence and the sharedsecret key generated at the controller matches the first hash code.

In yet another aspect, the invention features a mouthpiece for providingneurorehabilitation to a patient, the mouthpiece receiving electricalneurostimulation signals from a controller and selectively deliveringthe received electrical neurostimulation signals to the patient. Themouthpiece includes an elongated housing having an anterior region and aposterior region, the elongated housing having a non-planar exterior topsurface. The mouthpiece also includes a printed circuit board mounted toa bottom portion of the elongated housing, the printed circuit boardhaving a plurality of electrodes for delivering subcutaneous localelectrical stimulation to the patient's tongue. The mouthpiece alsoincludes control circuitry mounted within a top portion of the elongatedhousing for controlling electrical signals delivered to the electrodes.The mouthpiece also includes a memory mounted within the top portion ofthe elongated housing. The mouthpiece also includes a processor mountedwithin the top portion of the elongated housing, the processorconfigured to (i) store a first hash code and a unique serial number,the first hash code based on the unique serial number and a sharedsecret key (ii) transmit the first hash code and the unique serialnumber to the controller, (iv) receive communications from thecontroller only if a second hash code based on the unique serial numberand the shared secret key generated at the controller matches the firsthash code. In some embodiments, the first hash code is an SHA-256 hashcode.

In yet another aspect, the invention features a system for providingnon-invasive neuromodulation to a patient. The system includes amouthpiece and a controller. The mouthpiece includes an elongatedhousing having an anterior region and a posterior region, the elongatedhousing having a non-planar exterior top surface. The mouthpiece alsoincludes a printed circuit board mounted to a bottom portion of theelongated housing, the printed circuit board having a plurality ofelectrodes for delivering subcutaneous local electrical stimulation tothe patient's tongue. The mouthpiece also includes control circuitrymounted within a top portion of the elongated housing for controllingelectrical signals delivered to the electrodes. The mouthpiece alsoincludes a cable with a first end attached to the anterior portion ofthe elongated housing and having a connector at a second end forconnecting to a controller, the cable delivering electrical current tothe electrodes via the control circuitry. The controller includes anelongated u-shaped element having first and second arms that separate ananterior portion from a posterior portion, the anterior portion of theelongated u-shaped element located at a first distance from one of thearms and having a first mass, and the posterior portion of the elongatedu-shaped element located at a second distance from the other of the armsand having a second mass, the product of the first mass and the firstdistance being larger than the product of the second mass and the seconddistance. The controller also includes an electronic receptacle locatedat the anterior portion of the u-shaped element connecting to the cable.The controller also includes a microcontroller located within thethree-dimensional u-shaped element, the microcontroller configured tosend electrical control signals to the mouthpiece, the electricalcontrol signals determining an amplitude and duration of electricalsignals delivered to the patient's tongue.

In some embodiments, the width of the elongated-u-shaped elementcorresponds to approximately the 60^(th) percentile of adult male neckwidths. In some embodiments, the length of the elongated-u-shapedelement is approximately 200 mm. In some embodiments, the width of theelongated-u-shaped element is approximately 120 mm. In some embodiments,the anterior portion includes a first portion having a first width ofapproximately 35 mm and a second portion having a second width ofapproximately 35 mm, the first portion being attached to the first arm,and the second portion being attached to the second arm. In someembodiments, the first mass is greater than the second mass. In someembodiments, the first mass is smaller than the second mass. In someembodiments, the first and second distances are determined based on aportion of the arms configured to contact a patient's shoulders. In someembodiments, the arms have a radius of curvature in the range of 20-30cm in a sagittal plane of the patient to cause the controller tosubstantially conform to a patient's shoulders. In some embodiments, thewidth of the elongated u-shaped element is between 60% and 80% of thelength of the elongated u-shaped element. In some embodiments, the widthof the elongated u-shaped element is approximately 60% of the length ofthe elongated u-shaped element. In some embodiments, an interior contourof the posterior portion has a radius of curvature in the range of 20-60mm in a transverse plane of the patient. In some embodiments, aninterior contour of the posterior portion has a radius of curvature ofapproximately 40 mm in a transverse plane of the patient. In someembodiments, an exterior contour of the posterior portion has a radiusof curvature in the range of 10-40 mm in a transverse plane of thepatient. In some embodiments, an exterior contour of the posteriorportion has a radius of curvature of approximately 25 mm in a transverseplane of the patient. In some embodiments, a contour of the first andsecond arms has a radius of curvature in the range of 330-430 mm in atransverse plane of the patient. In some embodiments a contour of thefirst and second arms has a radius of curvature of approximately 380 mmin a transverse plane of the patient. In some embodiments, the anteriorportion includes an opening having a width in the range of 30-60 mm. Insome embodiments, the anterior portion includes an opening having awidth of approximately 45 mm. In some embodiments, the system includesan accelerometer for measuring an activity level of the patient. In someembodiments, the system includes a data logger for logging informationrelated to the activity level of the patient. In some embodiments, thesystem includes tongue sense circuitry for determining if a patient'stongue is in contact with the plurality of electrodes located on thebottom portion of the mouthpiece. In some embodiments, the systemincludes a clock for determining a total time of usage of themouthpiece. In some embodiments, the system includes a battery forproviding a current to the mouthpiece. In some embodiments, the systemincludes an optical indicator that indicates a power level of thebattery. In some embodiments, the system includes an audio indicatorthat can warn the patient when the remaining battery charge isinadequate to complete a therapy session.

In yet another aspect, the invention features a system for providingnon-invasive neuromodulation to a patient. The system includes amouthpiece and a controller. The mouthpiece includes an elongatedhousing having an anterior region and a posterior region, the elongatedhousing having a non-planar exterior top surface. The mouthpiece alsoincludes a printed circuit board mounted to the elongated housing, theprinted circuit board having a plurality of electrodes for deliveringsubcutaneous local electrical stimulation to the patient's tongue. Themouthpiece also includes control circuitry mounted within the elongatedhousing for controlling electrical signals delivered to the electrodes.The mouthpiece also includes a first communication module deliveringelectrical current to the electrodes via the control circuitry. Thecontroller includes an elongated u-shaped element having first andsecond arms that separate an anterior portion from a posterior portion,the anterior portion of the elongated u-shaped element located at afirst distance from one of the arms and having a first mass, and theposterior portion of the elongated u-shaped element located at a seconddistance from the other of the arms and having a second mass, theproduct of the first mass and the first distance being larger than theproduct of the second mass and the second distance. The controller alsoincludes a second communication module within the housing coupled to andin communication with the first communication module. The controlleralso includes a microcontroller located within the housing andconfigured to exchange electrical signals with the mouthpiece, theelectrical signals determining an amplitude and duration ofelectrostimulation energy pulses delivered to the patient's tongue.

In some embodiments, the system includes an accelerometer for measuringan activity level of the patient. In some embodiments, the systemincludes a data logger for logging information related to the activitylevel of the patient. In some embodiments, the system includes tonguesense circuitry for determining if a patient's tongue is in contact withthe plurality of electrodes located on the bottom portion of themouthpiece. In some embodiments, the system includes a clock fordetermining a total time of usage of the mouthpiece. In someembodiments, the system includes a battery for providing a current tothe mouthpiece. In some embodiments, the system includes an opticalindicator that indicates a power level of the battery. In someembodiments, the system includes an audio indicator that can warn thepatient when the remaining battery charge is inadequate to complete atherapy session. In some embodiments, the width of theelongated-u-shaped element corresponds to approximately the 60^(th)percentile of adult male neck widths. In some embodiments, the length ofthe elongated-u-shaped element is approximately 200 mm. In someembodiments, the width of the elongated-u-shaped element isapproximately 120 mm. In some embodiments, the anterior portion includesa first portion having a first width of approximately 35 mm and a secondportion having a second width of approximately 35 mm, the first portionbeing attached to the first arm, and the second portion being attachedto the second arm. In some embodiments, the first mass is greater thanthe second mass. In some embodiments, the first mass is smaller than thesecond mass. In some embodiments, the first and second distances aredetermined based on the location of the arms configured to contact apatient's shoulders. In some embodiments, the first and second distancesare determined based on a portion of the arms configured to contact apatient's shoulders. In some embodiments, the arms have a radius ofcurvature of in the range of 20 to 30 cm in a sagittal plane of thepatient to cause the controller to substantially conform to a patient'sshoulders. In some embodiments, the width of the elongated u-shapedelement is between 60% and 80% of the length of the elongated u-shapedelement. In some embodiments, the width of the elongated u-shapedelement is approximately 60% of the length of the elongated u-shapedelement. In some embodiments, an interior contour of the posteriorportion has a radius of curvature in the range of 20-60 mm in atransverse plane of the patient. In some embodiments, an interiorcontour of the posterior portion has a radius of curvature ofapproximately 40 mm in a transverse plane of the patient. In someembodiments, an exterior contour of the posterior portion has a radiusof curvature in the range of 10-40 mm in a transverse plane of thepatient. In some embodiments, an exterior contour of the posteriorportion has a radius of curvature of approximately 25 mm in a transverseplane of the patient. In some embodiments, a contour of the first andsecond arms has a radius of curvature in the range of 330-430 mm in atransverse plane of the patient. In some embodiments, a contour of thefirst and second arms has a radius of curvature of approximately 380 mmin a transverse plane of the patient. In some embodiments, the anteriorportion includes an opening having a width in the range of 30-60 mm. Insome embodiments, the anterior portion includes an opening having awidth of approximately 45 mm.

As used herein, the terms “approximately,” “roughly,” and“substantially” mean±10%, and in some embodiments, ±5%. Referencethroughout this specification to “one example,” “an example,” “oneembodiment,” or “an embodiment” means that a particular feature,structure, or characteristic described in connection with the example isincluded in at least one example of the present technology. Thus, theoccurrences of the phrases “in one example,” “in an example,” “oneembodiment,” or “an embodiment” in various places throughout thisspecification are not necessarily all referring to the same example.Furthermore, the particular features, structures, routines, steps, orcharacteristics may be combined in any suitable manner in one or moreexamples of the technology. The headings provided herein are forconvenience only and are not intended to limit or interpret the scope ormeaning of the claimed technology.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages of the invention described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. Thedrawings are not necessarily to scale, emphasis instead generally beingplaced upon illustrating the principles of the invention.

FIG. 1 is a drawing of a patient engaged in a non-invasiveneurostimulation therapy session according to an illustrative embodimentof the invention.

FIGS. 2A and 2B are diagrams showing a neurostimulation system accordingto an illustrative embodiment of the invention.

FIG. 2C is a diagram showing a neurostimulation system according to anillustrative embodiment of the invention.

FIG. 3A is a diagram showing a more detailed view of theneurostimulation system depicted in FIGS. 2A and 2B.

FIG. 3B is a diagram showing a more detailed view of theneurostimulation system depicted in FIG. 2C.

FIG. 3C is a diagram showing a more detailed view of an electrode array.

FIG. 3D is a graph showing an exemplary sequence of pulses for effectingneurostimulation of a patient.

FIG. 4A is a flow chart illustrating a method in accordance with oneembodiment for operating a neurostimulation system.

FIG. 4B is a flow chart illustrating a method in accordance with oneembodiment for operating a neurostimulation system.

FIG. 5A is a diagram showing a neurostimulation system according to anillustrative embodiment of the invention.

FIG. 5B is a diagram showing a controller according to an illustrativeembodiment of the invention.

FIG. 5C is a flow chart illustrating a method in accordance with oneembodiment for operating a neurostimulation system.

FIGS. 6A and 6B are diagrams showing a neurostimulation system accordingto an illustrative embodiment of the invention.

FIGS. 7A and 7B are diagrams showing a neurostimulation system accordingto an illustrative embodiment of the invention.

FIGS. 8A and 8B are diagrams showing a neurostimulation system accordingto an illustrative embodiment of the invention.

FIG. 9A is a flow chart illustrating a method in accordance with oneembodiment for operating a neurostimulation system.

FIG. 9B is a flow chart illustrating a method in accordance with oneembodiment for operating a neurostimulation system.

FIGS. 10A-10D are diagrams showing a controller according to anillustrative embodiment of the invention.

DETAILED DESCRIPTION

FIG. 1 shows a patient 101 undergoing non-invasive neuromodulationtherapy (NINM) using a neurostimulation system 100. During a therapysession, the neurostimulation system 100 non-invasively stimulatesvarious nerves located within the patient's oral cavity, including atleast one of the trigeminal and facial nerves. In combination with theNINM, the patient engages in an exercise or other activity specificallydesigned to assist in the neurorehabilitation of the patient. Forexample, the patient can perform a physical therapy routine (e.g.,moving an affected limb, or walking on a treadmill) engage in a mentaltherapy (e.g., meditation or breathing exercises), or a cognitiveexercise (e.g., computer assisted memory exercises) during theapplication of NINM. The combination of NINM with an appropriatelychosen exercise or activity has been shown to be useful in treating arange of maladies including, for example, traumatic brain injury, stroke(TBI), multiple sclerosis (MS), balance, gait, vestibular disorders,visual deficiencies, tremor, headache, migraines, neuropathic pain,hearing loss, speech recognition, auditory problems, speech therapy,cerebral palsy, blood pressure, relaxation, and heart rate. For example,a useful non-invasive neuromodulation (NINM) therapy routine has beenrecently developed as described in U.S. Pat. No. 8,849,407, the entiretyof which is incorporated herein by reference.

FIGS. 2A and 2B show a non-invasive neurostimulation system 100. Thenon-invasive neurostimulation system 100 includes a controller 120 and amouthpiece 140. The controller 120 includes a receptacle 126 andpushbuttons 122. The mouthpiece 140 includes an electrode array 142 anda cable 144. The cable 144 connects to the receptacle 126, providing anelectrical connection between the mouthpiece 140 and the controller 120.In some embodiments, the controller 120 includes a cable. In someembodiments, the mouthpiece 140 and the controller 120 are connectedwirelessly (e.g., without the use of a cable). During operation, apatient activates the neurostimulation system 100 by actuating one ofthe pushbuttons 122. In some embodiments, the neurostimulation system100 periodically transmits electrical pulses to determine if theelectrode array 142 is in contact with the patient's tongue andautomatically activates based on the determination. After activation,the patient can start an NINM treatment session, stop the NINM treatmentsession, or pause the NINM treatment session by pressing one of thepushbuttons 122. In some embodiments, the neurostimulation system 100periodically transmits electrical pulses to determine if the electrodearray 142 is in contact with the patient's tongue and automaticallypauses the NINM treatment session based on the determination. During anNINM treatment session, the patient engages in an exercise or otheractivity designed to facilitate neurorehabilitation. For example, duringan NINM treatment session, the patient can engage in a physicalexercise, a mental exercise, or a cognitive exercise. In someembodiments, the controller 120 has pushbuttons on both arms. In someembodiments, a mobile device can be used in conjunction with thecontroller 120 and the mouthpiece 140. The mobile device can include asoftware application that allows a user to activate the neurostimulationsystem 100 and start or stop an NINM treatment session by for example,pressing a button on the mobile device, or speaking a command into themobile device. The mobile device can obtain patient information andtreatment session information before, during, or after an NINM treatmentsession. In some embodiments, the controller 120 includes a securecryptoprocessor that holds a secret key, to be described in more detailbelow in connection with FIGS. 9A and 9B. The secure cryptoprocessor isin communication with a microcontroller. The secure cryptoprocessor canbe tamper proof. For example, if outer portions of the cryptoprocessorare removed in an attempt to access the secret key, the cryptoprocessorerases all memory, preventing unauthorized access of the secret key.

FIG. 2C shows a non-invasive neurostimulation system 100. As shown, amobile device 121 is in communication with a mouthpiece 140. Morespecifically, the mobile device 121 includes a processor running asoftware application that facilitates communications with the mouthpiece140. The mobile device 121 can be, for example, a mobile phone, aportable digital assistant (PDA), or a laptop. The mobile device 121 cancommunicate with the mouthpiece 140 by a wireless or wired connection.During operation, a patient activates the neurostimulation system 100via the mobile device 121. After activation, the patient can start anNINM treatment session, stop the NINM treatment session, or pause theNINM treatment session by manipulating the mobile device 121. During anNINM treatment session, the patient engages in an exercise or activitydesigned to provide neurorehabilitation. For example, during an NINMtreatment session, the patient can engage in a physical exercise, amental exercise, or a cognitive exercise.

FIG. 3A shows the internal circuitry housed within the controller 120.The circuitry includes a microcontroller 360, isolation circuitry 379, auniversal serial bus (USB) connection 380, a battery managementcontroller 382, a battery 362, a push-button interface 364, a display366, a real time clock 368, an accelerometer 370, drive circuitry 372,tongue sense circuitry 374, audio feedback circuitry 376, vibratoryfeedback circuitry 377, and a non-volatile memory 378. The drivecircuitry 372 includes a multiplexor, and an array of resistors tocontrol voltages delivered to the electrode array 142. Themicrocontroller 360 is in electrical communication with each of thecomponents shown in FIG. 3A. The isolation circuitry 379 provideselectrical isolation between the USB connection 380 and all othercomponents included in the controller 120. Additionally, the circuitryshown in FIG. 3A is in communication with the mouthpiece 140 via theexternal cable 144. During operation, the microcontroller 360 receiveselectrical power from battery 362 and can store and retrieve informationfrom the non-volatile memory 378. The battery can be charged via the USBconnection 380. The battery management circuitry controls the chargingof the battery 362. A patient can interact with the controller 120 viathe push-button interface 122 that converts the patient's pressing of abutton (e.g. an info button, a power button, an intensity-up button, anintensity-down button, and a start/stop button) into an electricalsignal that is transmitted to the microcontroller 360. For example, atherapy session can be started when the patient presses a start/stopbutton after powering on the controller 120. During the therapy session,the drive circuitry 372 provides an electrical signal to the mouthpiece140 via the cable 144. The electrical signal is communicated to thepatient's intraoral cavity via the electrode array 142. Theaccelerometer 370 can be used to provide information about the patient'smotion during the therapy session. Information provided by theaccelerometer 370 can be stored in the non-volatile memory 378 at acoarse or detailed level. For example, a therapy session aggregatemotion index can be stored based on the number of instances whereacceleration rises above a predefined threshold, with or without lowpass filtering. Alternatively, acceleration readings could be stored ata predefined sampling interval. The information provided by theaccelerometer 370 can be used to determine if the patient is engaged ina physical activity. Based on the information received from theaccelerometer 370, the microcontroller 360 can determine an activitylevel of the patient during a therapy session. For example, if thepatient engages in a physical activity for 30 minutes during a therapysession, the accelerometer 370 can periodically communicate (e.g. onceevery second) to the microcontroller 360 that the sensed motion islarger than a predetermined threshold (e.g. greater than 1 m/s²). Insome embodiments, the accelerometer data is stored in the non-volatilememory 378 during the therapy session and transmitted to the mobiledevice 121 after the therapy session has ended. After the therapysession has ended, the microcontroller 360 can record the amount of timeduring the therapy session in which the patient was active. In someembodiments, the recorded information can include other data about thetherapy session (e.g., the date and time of the session start, theaverage intensity of electrical neurostimulation delivered to thepatient during the session, the average activity level of the patientduring the session, the total session time the mouthpiece has been inthe patient's mouth, the total session pause time, the number of sessionshorting events, and/or the length of the session or the type ofexercise or activity performed during the therapy session) and can betransmitted to a mobile device. A session shorting event can occur ifthe current transmitted from the drive circuitry to the electrode array142 exceeds a predetermined threshold or if the charge transmitted fromthe drive circuitry to the electrode array exceeds a predeterminedthreshold over a predetermined time interval. After a session shortingevent has occurred, the patient must manually press a pushbutton toresume the therapy session. The real time clock (RTC) 368 provides timeand date information to the microcontroller 360. In some embodiments,the controller 120 is authorized by a physician for a predeterminedperiod of time (e.g., two weeks). The RTC 368 periodically communicatesdate and time information to the microcontroller 360. In someembodiments, the RTC 368 is integrated with the microcontroller. In someembodiments, the RTC 368 is powered by the battery 362, and upon failureof the battery 362, the RTC 368 is powered by a backup battery. Afterthe predetermined period of time has elapsed, the controller 120 can nolonger initiate the delivery of electrical signals to the mouthpiece 140and the patient must visit the physician to reauthorize use of thecontroller 120. The display 366 displays information received by themicrocontroller 360 to the patient. For example, the display 366 candisplay the time of day, therapy information, battery information, timeremaining in a therapy session, error information, and the status of thecontroller 120. The audio feedback circuitry 376 and vibratory feedbackcircuitry 377 can give feedback to a user when the device changes state.For example, when a therapy session begins, the audio feedback circuitry376 and the vibratory feedback circuitry 377 can provide auditory and/orvibratory cues to the patient, notifying the patient that the therapysession has been initiated. Other possible state changes that maytrigger audio and/or vibratory cues include pausing a therapy session,resuming a therapy session, the end of a timed session, canceling atimed session, or error messaging. In some embodiments, a clinician canturn off one or more of the auditory or vibratory cues to tailor thefeedback to an individual patient's needs. The tongue sense circuitry374 measures the current passing from the drive circuitry to theelectrode array 142. Upon sensing a current above a predeterminedthreshold, the tongue sense circuitry 374 presents a high digital signalto the microcontroller 360, indicating that the tongue is in contactwith the electrode array 142. If the current is below the predeterminedthreshold, the tongue sense circuitry 374 presents a low digital signalto the microcontroller 360, indicating that the tongue is not in contactor is in partial contact with the electrode array 142. The indicationsreceived from the tongue sense circuitry 374 can be stored in thenon-volatile memory 378. In some embodiments, the display 366 can be anorganic light emitting diode (OLED) display. In some embodiments, thedisplay 366 can be a liquid crystal display (LCD). In some embodiments,a display 366 is not included with the controller 120. In someembodiments, neither the controller 120 nor the mouthpiece 140 includesa cable, and the controller 120 communicates wirelessly with themouthpiece 140. In some embodiments, neither the controller 120 nor themouthpiece 140 includes an accelerometer. In some embodiments, the drivecircuitry 372 is located within the mouthpiece. In some embodiments, aportion of the drive circuitry 372 is located within the mouthpiece 140and a portion of the drive circuitry 372 is located within thecontroller 120. In some embodiments, neither the controller 120 nor themouthpiece 140 includes tongue sense circuitry 374. In some embodiments,the mouthpiece 140 includes a microcontroller and a multiplexer.

FIG. 3B shows a more detailed view of FIG. 2C. The mouthpiece 140includes a battery 362, tongue sense circuitry 374, an accelerometer370, a microcontroller 360, drive circuitry 372, a non-volatile memory378, a universal serial bus controller (USB) 380, and battery managementcircuitry 382. During operation, the microcontroller receives electricalpower from battery 362 and can store and retrieve information from thenon-volatile memory 378. The battery can be charged via the USBconnection 380. The battery management circuitry 382 controls thecharging of the battery 362. A patient can interact with the mouthpiece140 via the mobile device 121. The mobile device 121 includes anapplication (e.g. software running on a processor) that allows thepatient to control the mouthpiece 140. For example, the application caninclude an info button, a power button an intensity-up button, anintensity-down button, and a start/stop button that are presented to theuser visually via the mobile device 121. When the patient presses abutton presented by the application running on the mobile device 121, asignal is transmitted to the microcontroller 360 housed within themouthpiece 140. For example, a therapy session can be started when thepatient presses a start/stop button on the mobile device 121. During thetherapy session, the drive circuitry 372 provides an electrical signalto an electrode array 142 located on the mouthpiece 140. Theaccelerometer 370 can be used to provide information about the patient'smotion during the therapy session. The information provided by theaccelerometer 370 can be used to determine if the patient is engaged ina physical activity. Based on the information received from theaccelerometer 370, the microcontroller 360 can determine an activitylevel of the patient during a therapy session. For example, if thepatient engages in a physical activity for 30 minutes during a therapysession, the accelerometer 370 can periodically communicate (e.g. onceevery second) to the microcontroller 360 that the sensed motion islarger than a predetermined threshold (e.g. greater than 1 m/s²). Afterthe therapy session has ended, the microcontroller 360 can record theamount of time during the therapy session in which the patient wasactive. In some embodiments, the accelerometer 370 is located within themobile device 121 and the mobile device 121 determines an activity levelof a patient during the therapy session based on information receivedfrom the accelerometer 370. The mobile device can then record the amountof time during the therapy session in which the patient was active. Themobile device 121 includes a real time clock (RTC) 368 that providestime and date information to the microcontroller 360. In someembodiments, the mouthpiece 140 is authorized by a physician for apredetermined period of time (e.g., two weeks). After the predeterminedperiod of time has elapsed, the mouthpiece 140 can no longer deliverelectrical signals to the patient via the electrode array 142 and thepatient must visit the physician to reauthorize use of the mouthpiece140. In some embodiments, the mouthpiece 140 includes pushbuttons (e.g.,an on/off button) and a patient can manually operate the mouthpiece 140via the pushbuttons. After a therapy session, the mouthpiece 140 cantransmit information about the therapy session to a mobile device. Insome embodiments, the mouthpiece 140 does not include a USB controller380 and instead communicates only via wireless communications with thecontroller.

FIG. 3C shows a more detailed view of the electrode array 142. Theelectrode array 142 can be separated into 9 groups of electrodes,labelled a-i, with each group having 16 electrodes, except group b whichhas 15 electrodes. Each electrode within the group corresponds to one of16 electrical channels. During operation, the drive circuitry candeliver a sequence of electrical pulses to the electrode array 142 toprovide neurostimulation of at least one of the patient's trigeminal orfacial nerve. The electrical pulse amplitude delivered to each group ofelectrodes can be larger near a posterior portion of the tongue andsmaller at an anterior portion of the tongue. For example, the pulseamplitude of electrical signals delivered to groups a-c can be 19 voltsor 100% of a maximum value, the pulse amplitude of electrical signalsdelivered to groups d-f can be 14.25 volts or 75% of the maximum value,the pulse amplitude of electrical signals delivered to groups g-h can be11.4 volts or 60% of the maximum value, and the pulse amplitude ofelectrical signals delivered to group i can be 9.025 volts or 47.5% ofthe maximum value. In some embodiments, the maximum voltage is in therange of 0 to 40 volts. The pulses delivered to the patient by theelectrode array 142 can be random or repeating. The location of pulsescan be varied across the electrode array 142 such that differentelectrodes are active at different times, and the duration and/orintensity of pulses may vary from electrode. For oral tissuestimulation, currents of 0.5-50 mA and voltages of 1-40 volts can beused. In some embodiments, transient currents can be larger than 50 mA.The stimulus waveform may have a variety of time-dependent forms, andfor cutaneous electrical stimulation, pulse trains and bursts of pulsescan be used. Where continuously supplied, pulses may be 1-500microseconds long and repeat at rates from 1-1000 pulses/second. Wheresupplied in bursts, pulses may be grouped into bursts of 1-100pulses/burst, with a burst rate of 1-100 bursts/second.

In some embodiments, pulsed waveforms are delivered to the electrodearray 142. FIG. 3D shows an exemplary sequence of pulses that can bedelivered to the electrode array 142 by the drive circuitry 372. A burstof three pulses, each spaced apart by 5 ms is delivered to each of the16 channels. The pulses in neighboring channels are offset from oneanother by 312.5 μs. The burst of pulses repeats every 20 ms. The widthof each pulse can be varied from 0.3-60 μs to control an intensity ofneurostimulation (e.g., a pulse having a width of 0.3 μs will cause asmaller amount of neurostimulation than a pulse having a width of 60μs).

FIG. 4A shows a method of operation 400 of a controller 120 as describedin FIGS. 2A, 2B and 3A. A patient attaches a mouthpiece 140 to acontroller 120 (step 404). The patient turns on the controller 120 (step408) using, for example, a power button. The patient places thecontroller 120 around his/her neck (step 412) as shown in FIG. 1B. Thepatient places a mouthpiece 140 in his/her mouth (step 416). The patientinitiates a therapy session by pressing a start/stop button (step 420).During the therapy session, the controller 120 delivers electricalsignals to the mouthpiece 140. The patient calibrates the intensity ofthe electrical signals (step 424). The patient raises the intensity ofthe electrical signals delivered to the mouthpiece by pressing anintensity-up button until the neurostimulation is above the patient'ssensitivity level. The patient presses an intensity-down button untilthe neurostimulation is comfortable and non-painful. After thecalibration step, the patient performs a prescribed exercise (step 428).The exercise can be cognitive, mental, or physical. In some embodiments,physical exercise includes the patient attempting to maintain a normalposture or gait, the patient moving his/her limbs, or the patientundergoing speech exercises. Cognitive exercises can include “braintraining” exercises, typically computerized, that are designed torequire the use of attention span, memory, or reading comprehension.Mental exercises can include visualization exercises, meditation,relaxation techniques, and progressive exposure to “triggers” forcompulsive behaviors.

In some embodiments, the patient can rest for a period of time duringthe therapy session (e.g. the patient can rest for 2 minutes during a 30minute therapy session). After a predetermined period of time (forexample, thirty minutes) has elapsed, the therapy session ends (step432) and the controller 120 stops delivering electrical signals to themouthpiece 140. In some embodiments, the intensity of electrical signalsincreases from zero to the last use level selected by the patient over atime duration in the range of 1-5 seconds after the patient starts atherapy session by pressing the start/stop button. In some embodiments,the intensity of electrical signals is set to a fraction of the last uselevel selected by the patient (e.g. ¾ of the last level selected) afterthe patient starts a therapy session by pressing the start/stop button.In some embodiments, the intensity of electrical signals increases fromzero to a fraction of the last use level selected by the patient (e.g. ¾of the last level selected) over a time duration in the range of 1-5seconds after the patient starts a therapy session by pressing thestart/stop button. In some embodiments, the intensity of electricalsignals increases instantaneously from zero to the last use levelselected by the patient after the patient starts a therapy session bypressing the start/stop button.

In some embodiments, the mouthpiece 140 is connected to the controller120 after the controller 120 is turned on. In some embodiments, themouthpiece 140 is connected to the controller 120 after the controller120 is donned by the patient. In some embodiments, the patientcalibrates the intensity of the electrical signals before initiating atherapy session. In some embodiments, a patient performs an initialcalibration of the intensity of electrical signals in the presence of aclinician and does not calibrate the intensity of the electrical signalsduring subsequent treatments performed in the absence of a clinician.

FIG. 4B shows a method of operation 449 of the non-invasiveneurostimulation system 100 described in FIGS. 2C and 3B. A patientactivates a mobile device 121 (step 450). The patient places amouthpiece 140 in his/her mouth (step 454). The patient initiates atherapy session by pressing a start/stop button within an applicationrunning on the mobile device 121 (step 458). During the therapy session,circuitry within the mouthpiece 140 delivers electrical signals to anelectrode array 142 located on the mouthpiece 140. The patientcalibrates the intensity of the electrical signals (step 462). Thepatient first raises the intensity of the electrical signals deliveredto the mouthpiece 140 by pressing an intensity-up button located withinan application running on the mobile device 121 until theneurostimulation is above the patient's sensitivity level. The patientpresses an intensity-down button running within an application on themobile device 121 until the neurostimulation is comfortable andnon-painful. After the calibration step, the patient performs aprescribed exercise (step 464). The exercise can be cognitive, mental,or physical. In some embodiments, the patient can rest for a period oftime during the therapy session (e.g. the patient can rest for 5 minutesduring a 30 minute therapy session). After a predetermined period oftime (for example, thirty minutes) has elapsed, the therapy session ends(step 468) and the circuitry located within the mouthpiece 140 stopsdelivering electrical signals to the electrode array 142. In someembodiments, the calibration of the intensity of the electrical signalstakes place before the patient initiates a therapy session.

FIG. 5A shows a neurostimulation system 500 and FIG. 5B shows a backview of a controller 520. The neurostimulation system 500 includes acontroller 520 and a mouthpiece 540 connected via a cable 544. Themouthpiece 540 includes an electrode array on a bottom portion thereof.The controller 520 includes an anterior portion 560 and a posteriorportion 564. The controller 520 also includes a mouthpiece port 516, anintensity-up button 508, an intensity-down button 512, a power button521, an info button 524, a start/stop button 504 and a display 528. Themouthpiece 540 is in electrical communication with the controller 520via the cable 544. In some embodiments, the power button 521 includes alight emitting diode (LED) indicator. In some embodiments, the port 516is located on the mouthpiece 540 instead of the controller 520 and thecable 544 is permanently attached to the controller 520. In someembodiments the port is a universal serial bus (USB) port and/or acharging port.

FIG. 5C describes a method 200 of operating the neurostimulation system500 shown in FIGS. 5A and 5B. A patient activates the neurostimulationsystem 500 by pressing a power button 521 (step 208). After activation,the neurostimulation system 500 enters an idle state (step 212). Whilein the idle state, non-invasive neurostimulation is not delivered to thepatient. If the neurostimulation system 500 remains in the idle statefor a predetermined time period, the neurostimulation system 500 canshut down or enter a power-saving state (e.g., after idling for 10minutes). Additionally, if the power button 521 is pressed while in theidle state, the neurostimulation system 500 shuts down. If the patientpresses a start button (step 224), an NINM therapy session begins andnon-invasive neurostimulation generated by the controller 520 isdelivered to the patient's oral cavity via the mouthpiece 540 for apredetermined period of time. In some embodiments, the neurostimulationsystem 500 enters an intensity adjustment state when the patient pressesa start button (step 224). The patient then raises the intensity of theelectrical signals delivered to the mouthpiece by pressing theintensity-up button 508 until the neurostimulation is above thepatient's sensitivity level. The patient presses the intensity-downbutton 512 until the neurostimulation is comfortable and non-painful.After the intensity adjustment is completed, the patient presses thestart button again to begin an NINM therapy session. In one embodiment,the predetermined period of time can be in the user-selectable range of20-30 minutes. Additionally, the patient performs a physical, cognitive,or mental exercise during the NINM therapy session. The physical,cognitive, or mental exercise is performed simultaneously with thedelivery of electrical signals from the controller 520 to the mouthpiece540. If the patient presses a pause button (step 232) whileneurostimulation is being delivered, the therapy session is paused (step233) and the neurostimulation system 500 ceases to deliver non-invasiveneurostimulation to the patient's oral cavity. In some embodiments, ifthe neurostimulation system 500 loses contact with the patient's oralcavity (e.g. determined by tongue sensing circuitry), the therapysession is paused. If the patient presses unpause (step 234), thetreatment is resumed and non-invasive neurostimulation is againdelivered to the patient's intraoral cavity. If the patient presses thestop button while the neurostimulation system 500 is paused, or if thereis no patient input for more than a predetermined time, for example, twominutes (step 235) after the patient has pressed the pause button, theneurostimulation system 500 enters an idle state (step 212) and a“treatment ended due to pause timeout” message is presented by thedisplay 528. If the patient presses the stop button (step 240) whileneurostimulation is being delivered, the neurostimulation system 500enters an idle state (step 212) and a “treatment ended due to sessionstop” message is presented by the display 528. Alternatively, if theneurostimulation system 500 delivers neurostimulation to the patient forthe full predetermined period of time at step 240, the system enters anidle state at step 212 and a “full session completed” message ispresented by the display 528.

While the system is in the idle state at step 212, a number ofconditions can prevent the patient from initiating a therapy session.For example, if there is not enough charge remaining in the battery tocomplete at least one NINM therapy session, the controller 520 can blockthe patient from initiating the therapy session and a “low battery”message will be presented on the display 528. In some embodiments, thecontroller can emit an audible sound to alert the patient that there isnot enough charge remaining in the battery to complete at least one NINMtherapy session. Additionally, if the mouthpiece 540 is not attached tothe controller 520, the controller 520 can block the patient frominitiating a therapy session and a “no mouthpiece” message is presentedon the display 528.

In some embodiments, the neurostimulation system 500 deliversneurostimulation for a limited number of hours per day. For example, theneurostimulation system 500 can be configured to stop deliveringneurostimulation after 200 minutes of use in a single day. In the idlestate at step 212, if the daily limit has been exceeded, the controller520 can block the patient from initiating a therapy session and a “dailylimit reached” message is presented by the display 528. The patient canbegin treatment the next day (i.e., after midnight), when the dailylimit is reset.

In some embodiments, the neurostimulation system 500 deliversneurostimulation for a limited number of weeks. In the idle state atstep 212, if the calendar limit has been exceeded, the controller 520can block the patient from initiating a therapy session and a “calendarlimit reached” message is presented by the display 528. For example, theneurostimulation system 500 can be configured to stop deliveringneurostimulation 1-14 weeks after the patient receives theneurostimulation system 500 from a physician. To re-enable theneurostimulation system 500 after the calendar limit has been exceeded,the patient is required to visit a physician or a clinician. In someembodiments, a “calendar limit approaching” message is presented by thedisplay 528, warning the patient that the calendar limit will be reachedsoon (e.g. in two weeks). The “calendar limit approaching” message canbe beneficial to patients by allowing them to schedule appointments withtheir clinicians prior to the calendar limit being reached.

In some embodiments, the mouthpiece 540 can become damaged over time andrequire replacement. For example, the patient's bites down on themouthpiece 540 during each therapy session, slowly causing the surfaceof the mouthpiece to be damaged. This damage can cause the mouthpiece540 to malfunction. The average time to failure can be statisticallydetermined by testing a number of mouthpieces 540 over a number oftherapy sessions and examining the mouthpieces for damage at the end ofeach therapy session. The average time to failure, once determined, canbe programmed into the controller 520. During the idle state at step212, if the average time to failure has been reached, the controller 520can block the patient from initiating a therapy session and a“mouthpiece expired” message is presented by the display 528. In someembodiments, a message is presented by the display 528, warning thepatient that the mouthpiece is set to expire soon. For example, themessage presented by the display 528 can be “mouthpiece expires in 14days.”

In some embodiments, the display 528 can present an “authenticationerror” message if a mouthpiece 540 cannot be authenticated, for exampleas described in FIGS. 9A and 9B. In some embodiments, theneurostimulation system 500 tracks an activity level of a patient. Forexample, the neurostimulation system 500 can include an accelerometerthat detects an activity level of the patient (e.g., at rest, walking,or running). In some embodiments, the activity level can be recorded andstored on an external computer for analysis. For example, the recordedactivity level data can be analyzed by a physician to determine aneffectiveness of a prescribed treatment plan. In some embodiments, theneurostimulation system 500 sets an intensity level to 75% of the lastused intensity level when the treatment begins at step 228. In someembodiments, data including time stamps, intensity levels, data receivedfrom the accelerometer, and data received from the tongue sensecircuitry can be recorded and stored on an external computer or mobiledevice for analysis.

In some embodiments, the port 516 can facilitate charging of theneurostimulation system 500. For example, when the port 516 is connectedto a charging source, the neurostimulation system 500 enters a chargingstate. In the charging state, a “Charging” message is presented by thedisplay 528. Additionally, in the charging state, an LED can indicate aremaining battery charge. For example, the LED can emit flashing redlight if there is not sufficient battery charge for at least one NINMtherapy session. If there is sufficient battery charge remaining tocomplete at least one NINM therapy session, the LED can emit flashinggreen. When the battery charging is complete, the LED can emit a solidgreen light (e.g. a non-flashing green light). While theneurostimulation system 500 is in the charging state, the patient cannotbegin an NINM therapy session. When the port is disconnected in thecharging state, the neurostimulation system 500 enters an idle state(step 212).

In some embodiments, an LED included with the power button 521 canindicate a remaining battery charge. For example, the LED can emit greenlight if there is sufficient battery charge remaining to complete two ormore NINM therapy sessions. If there is sufficient battery chargeremaining to complete one NINM therapy session, the LED can emit yellowlight. If there is not enough charge remaining for one NINM therapysession, the LED can emit red light. In some embodiments, the controller520 includes LEDs for providing visual indication, an audio indicator,or a vibratory indicator that can provide indications to the patient.For example, the LEDs, the audio indicator, and the vibratory indicatorcan provide an indication to the patient if electrical neurostimulationis being delivered to the mouthpiece 540, if electrical neurostimulationdelivery to the mouthpiece 540 has been disabled or cancelled, or if theNINM therapy session has ended. The indications can include a solid orflashing light emitted by the LEDs or a predetermined sound such as aring, buzz, or chirp emitted by the audio indicator. The vibratoryindicator can provide tactile feedback or other vibratory feedback tothe patient. In some embodiments, the audio and/or vibratory indicatorincludes a piezoelectric element or a magnetic buzzer that vibrates andprovides a mechanical indication to the patient. In some embodiments,the LEDs and/or the audio indicator provide an indication when an NINMtherapy session is 50% complete. In some embodiments, the LEDs and/orthe audio indicator provide an indication when any button on thecontroller 520 is pressed by the patient. In some embodiments, the LEDsand/or the audio indicator provide an indication of the intensity levelof the electrical neurostimulation. In some embodiments, the LEDs and/orthe audio indicator provide an indication of the remaining NINM therapysession time. In some embodiments, the LEDs and/or the audio indicatorprovide an indication of the remaining stimulation minutes for thecurrent day (e.g., before a daily limit is reached). In someembodiments, the LEDs and/or the audio indicator provide an indicationof the remaining stimulation minutes for the current calendar period(e.g., before a calendar limit is reached). In some embodiments,pressing a start/stop/pause button while neurostimulation is beingdelivered pauses the therapy session (step 233) and the neurostimulationsystem 500 ceases to deliver non-invasive neurostimulation to thepatient's oral cavity.

FIGS. 6A and 6B show a non-invasive neurostimulation system 600. Thenon-invasive neurostimulation system 600 includes headband 618, acontroller 620, pushbuttons 622, a display 628, a mouthpiece 640, anelectrode array 642, and a cable 624. The controller 620 is inelectrical communication with the mouthpiece 640 and the electrode array642 via the cable 624. During operation, a patient rests the headband618 along his/her ears and inserts the mouthpiece 640 into his/hermouth. Operation of the non-invasive neurostimulation system 600 issimilar to that described above in reference to FIGS. 5A and 5B wheresimilarly referenced elements have the same functionality (e.g.controller 620 has the same functionality as controller 520 etc.). Insome embodiments, the headband 618 maintains an orientation of themouthpiece 640 within the patient's mouth during an NINM therapysession. In some embodiments, the headband 618 maintains the position ofthe mouthpiece 640 within the patient's mouth, even if the patient is ina horizontal orientation or is upside-down.

FIGS. 7A and 7B show a non-invasive neurostimulation system 700. Thenon-invasive neurostimulation system 700 includes headband 718, acontroller 720, an intensity setting wheel 722, a mouthpiece 740, anelectrode array 742, and a cable 724. The controller 720 is inelectrical communication with the mouthpiece 740 and the electrode array742 via the cable 724. During operation, a patient rests the headband718 along an upper circumference of his/her head and inserts themouthpiece 740 into his/her mouth. The patient can increase theintensity of the electrical signals delivered to the mouthpiece 740 byrotating the intensity setting wheel in a clockwise direction. Thepatient can decrease the intensity of the electrical signals deliveredto the mouthpiece 740 by rotating the intensity setting wheel in acounterclockwise direction. Operation of the non-invasiveneurostimulation system 700 is otherwise similar to that described abovein reference to FIGS. 5A and 5B where similarly referenced elements havethe same functionality (e.g. controller 720 has the same functionalityas controller 520 etc.). In some embodiments, the headband 718 isconfigured to allow the patient to wear his/her glasses during an NINMtherapy session.

FIGS. 8A and 8B show a non-invasive neurostimulation system 800. Thenon-invasive neurostimulation system 800 includes a controller 820, amouthpiece 840, pushbuttons 822, display screen 828, and indicator light832. The controller 820 and the mouthpiece 840 are integrated into amonolithic package. The controller 820 is in electrical communicationwith the mouthpiece 840 and the electrode array 842. During operation, apatient inserts the mouthpiece 840 into his/her mouth and the rigidlyattached controller 820 rests just outside of the patient's mouth.Operation of the non-invasive neurostimulation system 800 is otherwisesimilar to that described above in reference to FIGS. 5A and 5B wheresimilarly referenced elements have the same functionality (e.g.controller 820 has the same functionality as controller 520 etc.). Insome embodiments, the controller 820 is in mechanical contact with thepatient's chin and is configured to mechanically secure the mouthpiece840 during an NINM therapy session. In some embodiments, a displayscreen 828 is not included with non-invasive neurostimulation system800. In some embodiments, a display screen 828 is replaced with anauditory indicator that provides auditory messages to the patient. Insome embodiments, the controller 820 and the mouthpiece 840 are eachmonolithic and connected at a connection point between the mouthpiece840 and the controller 820. In some embodiments, the mouthpiece 840 isremovably attached to the controller 820 and can be replaced atpredetermined usage intervals or upon wearing out.

FIG. 9A shows a method of operation 900 of the non-invasiveneurostimulation device illustrated in FIGS. 5-8. Initially a patientconnects a mouthpiece to a controller or mobile device (step 904). Theconnection can be a wired or wireless connection. A processor within thecontroller or mobile device generates a numeric sequence and transmitsthe generated sequence to the mouthpiece (step 908). The numericsequence generated at step 908 can be a sequence of random values,produced by a software pseudorandom number generator, or by a hardwarerandom number generator. Based on the received numeric sequence and asecret key shared between the mouthpiece and the controller, a processorlocated within the mouthpiece generates a first hash code (step 912).The first hash code can be generated using an HMAC (keyed-hash messageauthentication code) algorithm. In some embodiments, the first hash codeis generated in accordance with an SHA-256 algorithm. The mouthpiecethen transmits the first hashcode to the controller (step 916). Aprocessor located within the controller generates a second hash codebased on the shared secret key and the numeric sequence (step 920) andthen compares the first hash code with the second hash code (step 924).The numeric sequence generated at step 920 can be a sequence of randomvalues, produced by a software pseudorandom number generator, or by ahardware random number generator. In some embodiments, the second hashcode is generated in accordance with an SHA-256 algorithm. If the firsthash code matches the second hash code, then electrical communicationsare enabled between the controller and the mouthpiece (step 928). Thepatient then inserts the mouthpiece into his/her mouth bringing themouthpiece into contact with the patient's intraoral cavity (step 932).Electrical neurostimulation signals can then be delivered by thecontroller via the mouthpiece to the patient's intraoral cavity (step936).

FIG. 9B shows another method of operation 939 of the non-invasiveneurostimulation device as shown in FIGS. 5-8 in accordance with anembodiment of the invention. Initially, a patient connects a mouthpieceto a controller or mobile device (step 940). The connection can be awired or wireless connection. At the time of manufacture, a first hashcode is generated based on a unique serial number and a secret keyshared between the mouthpiece and the controller (step 944). The firsthash code can be generated by an HMAC (keyed-hash message authenticationcode) algorithm. In some embodiments, the first hash code is generatedin accordance with an SHA-256 algorithm. The first hash code and theunique serial number are stored in memory within the mouthpiece. Themouthpiece then transmits the first hash code and the unique serialnumber to the controller (step 948). The controller generates a secondhash code based on the received unique serial number and the sharedsecret key (step 952). The second hash code can be generated by an HMAC(keyed-hash message authentication code) algorithm. In some embodiments,the second hash code is generated in accordance with an SHA-256algorithm. The controller then compares the second hash code and thefirst hash code. The controller only permits continued electricalcommunications with the mouthpiece if the second hash code and the firsthash code match (step 956). The patient then inserts the mouthpiece intohis/her mouth bringing the mouthpiece into contact with the patient'sintraoral cavity (step 960). Electrical neurostimulation signals canthen be delivered by the controller via the mouthpiece to the patient'sintraoral cavity (step 964).

FIGS. 10A-10D shows a controller 1020 that is configured tosubstantially conform to a patient's shoulders and/or neck regions asshown in FIG. 1. The controller 1020, having a length L (e.g., in someembodiments the length L can be in the range of 180-250 mm), includes ananterior portion 1060, a posterior portion 1064, and two arms 1062 thatprovide a separation between the anterior portion 1060 and the posteriorportion 1064. The controller 1020 also includes a mouthpiece port 1016,an intensity-up button 1008, an intensity-down button 1012, a powerbutton 1021, an info button 1024, a start/stop button 1004 and a display1028. The posterior portion 1064 has a first radius of curvature 1034 ina transverse plane of a patient and a second radius of curvature 1036 inthe transverse plane of the patient. For example, in some embodimentsthe first radius of curvature 1034 can be in the range of 20-50 mm andthe second radius of curvature 1036 can be in the range of 15-35 mm. Thetwo arms 1062 are separated by a distance W₁, and have a first radius ofcurvature 1030 in a sagittal plane of the patient and a second radius ofcurvature 1032 in a transverse plane of the patient. For example, insome embodiments the first radius 1030 can be in the range of 100-400mm, the second radius of curvature 1032 can be in the range of 300-500mm, and the distance W₁ can be in the range of 90-150 mm. Each of thearms 1062 has a central portion 1050 that is configured to contact thepatient's neck and/or shoulders. The anterior portion 1060, having anopening with a width W₂, can have a first mass m₁ and be located at afirst distance d₁ from the central portion 1050 of the arms 1062 and theposterior portion 1064 can have a second mass m₂ and be located at asecond distance d₂ from the central portion 1050 of the arms 1062. Insome embodiments, m₁ can be in the range of 15-45 g and m₂ can be in therange of 50-80 g. In some embodiments, m₁ can be approximately 25 g andm₂ can be approximately 60 g. The distances d1, d2, and the masses m1,m2 can be chosen such that the controller conforms or substantiallyconforms to the patient's shoulders and/or neck as shown in FIG. 1. Insome embodiments, the product of d₁ and m₁ is larger than the product ofd₂ and m₂. In some embodiments, m₁ and m₂ are approximately equal and d₁is larger than d₂, such that m₁·d₁>m₂·d₂. In some embodiments, m₁ isless than m₂ and d₁ is larger than d₂, such that m₁·d₁>m₂·d₂. In someembodiments, m₁ is greater than m₂ and d₁ is larger than d₂, such thatm₁ d₁>m₂·d₂. In some embodiments, d₁ and d₂ are approximately equal andm₁ is larger than m₂, such that m₁·d₁>m₂·d₂. In some embodiments, d₁ isless than d₂ and m₁ is larger than m₂, such that m₁·d₁>m₂·d₂. In someembodiments, the first mass is in the range of 15-35 g, the second massis in the range of 60-65 g, the first distance is in the range of110-140 mm, and the second distance is in the range of 30-70 mm. In someembodiments, the ratio of the second mass to the first mass isapproximately 2.5 and the ratio of the first distance to the seconddistance is approximately 3. The controller 1020 operates similarly tocontroller 520 as described herein.

The terminology used herein is for the purpose of describing particularembodiments and is not intended to be limiting of the inventiveconcepts. It will be understood that, although the terms first, second,third etc. are used herein to describe various elements, components,regions, layers and/or sections, these elements, components, regions,layers and/or sections should not be limited by these terms. These termsare only used to distinguish one element, component, region, layer orsection from another element, component, region, layer or section. Thus,a first element, component, region, layer or section discussed belowcould be termed a second element, component, region, layer or sectionwithout departing from the teachings of the present application.

While the present inventive concepts have been particularly shown anddescribed above with reference to exemplary embodiments thereof, it willbe understood by those of ordinary skill in the art, that variouschanges in form and detail can be made without departing from the spiritand scope of the present inventive concepts described and defined by thefollowing claims.

What is claimed is:
 1. A system for providing neurorehabilitation to apatient, the system comprising a mouthpiece and a controller, themouthpiece receiving electrical neurostimulation signals from thecontroller and selectively delivering the received electricalneurostimulation signals to the patient, the mouthpiece comprising: anelongated housing having an anterior region and a posterior region, theelongated housing having a non-planar exterior top surface; a printedcircuit board mounted to a bottom portion of the elongated housing, theprinted circuit board having a plurality of electrodes for deliveringsubcutaneous local electrical stimulation to the patient's tongue;control circuitry mounted within a top portion of the elongated housingfor controlling electrical signals delivered to the electrodes; a memorymounted within a top portion of the elongated housing; and a processormounted within the top portion of the elongated housing, the processorconfigured to: (i) receive a numeric sequence from the controller, (ii)generate a first hash code based on the received numeric sequence and asecret key stored in the memory, wherein the secret key is sharedbetween the mouthpiece and the controller, (iii) transmit the first hashcode to the controller, and (iv) receive communications from thecontroller only if a second hash code based on the numeric sequence andthe shared secret key generated at the controller matches the first hashcode; and wherein the controller comprises: an elongated u-shapedelement configured to rest upon the patient's shoulders; an electronicreceptacle located at a terminus of the u-shaped element connecting tothe cable; a microcontroller located within the three-dimensionalu-shaped element, the microcontroller configured to send electricalcontrol signals to the mouthpiece, the electrical control signalsdetermining an amplitude and duration of electrical signals delivered tothe patient's tongue; and at least one of (i) an accelerometer formeasuring an activity level of the patient, (ii) a data logger forlogging information related to the activity level of the patient, (iii)tongue sense circuitry for determining if a patient's tongue is incontact with the plurality of electrodes located on the bottom portionof the mouthpiece, (iv) a clock for determining a total time of usage ofthe mouthpiece, or (v) an audio indicator that can warn the patient whenthe remaining battery charge is inadequate to complete a therapysession.
 2. The mouthpiece of claim 1 wherein the first hash code is anSHA-256 hash code.
 3. The mouthpiece of claim 1 wherein the second hashcode is an SHA-256 hash code.
 4. The system of claim 1 wherein thenumerical sequence comprises a sequence of random values.
 5. The systemof claim 4 further comprising a hardware random number generatorconfigured to generate the numerical sequence.
 6. A system for providingneurorehabilitation to a patient, the system comprising a mouthpiece anda controller, the mouthpiece receiving electrical neurostimulationsignals from the controller and selectively delivering the receivedelectrical neurostimulation signals to the patient, the mouthpiececomprising: an elongated housing having an anterior region and aposterior region, the elongated housing having a non-planar exterior topsurface; a printed circuit board mounted to a bottom portion of theelongated housing, the printed circuit board having a plurality ofelectrodes for delivering subcutaneous local electrical stimulation tothe patient's tongue; control circuitry mounted within a top portion ofthe elongated housing for controlling electrical signals delivered tothe electrodes; a memory mounted within the top portion of the elongatedhousing; and a processor mounted within the top portion of the elongatedhousing, the processor configured to (i) store a first hash code and aunique serial number, the first hash code based on the unique serialnumber and a secret key shared between the mouthpiece and thecontroller, (ii) transmit the first hash code and the unique serialnumber to the controller, and (iii) receive communications from thecontroller only if a second hash code based on the unique serial numberand the shared secret key generated at the controller matches the firsthash code; and wherein the controller comprises: an elongated u-shapedelement configured to rest upon the patient's shoulders; an electronicreceptacle located at a terminus of the u-shaped element connecting tothe cable; a microcontroller located within the three-dimensionalu-shaped element, the microcontroller configured to send electricalcontrol signals to the mouthpiece, the electrical control signalsdetermining an amplitude and duration of electrical signals delivered tothe patient's tongue; and at least one of (i) an accelerometer formeasuring an activity level of the patient, (ii) a data logger forlogging information related to the activity level of the patient, (iii)tongue sense circuitry for determining if a patient's tongue is incontact with the plurality of electrodes located on the bottom portionof the mouthpiece, (iv) a clock for determining a total time of usage ofthe mouthpiece, or (v) an audio indicator that can warn the patient whenthe remaining battery charge is inadequate to complete a therapysession.
 7. The mouthpiece of claim 6 wherein the first hash code is anSHA-256 hash code.
 8. The mouthpiece of claim 6 wherein the second hashcode is an SHA-256 hash code.
 9. The system of claim 6 wherein thenumerical sequence comprises a sequence of random values.
 10. The systemof claim 9 further comprising a hardware random number generatorconfigured to generate the numerical sequence.